~ Feb 07 Nutritional Strategies to Preserve Memory and Cognition

By Laurie Barclay, MD

In numerous studies, neuroscientists warn that the United States and other Western nations face a tidal wave of mind-destroying dementia that threatens to decimate the "golden years" of the soon-to-be-retired baby-boom generation.

In the US alone, dementia is already epidemic among the elderly: nearly one third of adults over the age of 80 are literally losing their minds.1,2 This shockingly high number is expected to skyrocket further in the coming decades.

More evidence that Alzheimer's is spreading like wildfire comes from the landmark Cognitive Function and Aging study, which found that fully one third of elderly subjects who died with no clinical signs of dementia had autopsy evidence of Alzheimer's disease. In other words, these adults were likely spared the afflictions of Alzheimer's only because they died of other causes before memory loss became apparent!3

The good news is, declining brain function during aging is not inevitable. In fact, "senile" dementias may merely reflect wholly preventable biochemical processes that are commonly seen with advancing age. Middle-aged adults who have yet to experience the onset of forgetfulness or mild cognitive impairment should act now to avoid it. Those who are already experiencing these symptoms should implement strategies to prevent the onset of full-blown dementia.3

Ensuring attention to enhanced brain nutrition may help preserve brain tissue and function with age. In this article, we present a two-pronged strategy that involves fueling brain cells with the nutrients needed for optimal nerve function, while quelling the inflammatory fires that ignite Alzheimer's disease and vascular dementia.4,5 Many of these nutrients are currently in use throughout Europe as prescription medications, but are available as dietary supplements in the US. Targeted nutritional strategies may well be our best bet for maintaining ideal brain health with aging and averting the coming epidemic of dementia.

Brain Nutrition Basics

There is still no cure for senile dementias once they develop, and our risk of acquiring these dreaded diseases climbs steeply with increasing age. Therefore, it is essential to take preventive action against cognitive decline as soon as possible.3,6 Fortunately, recent breakthroughs in understanding brain function—and how it is compromised both during aging and in specific dementias—can help us choose therapeutic agents that support robust brain health, even with advancing age.

Nutritional supplements that optimize cognitive health and function include those required for the synthesis and preservation of acetylcholine—a neurotransmitter central to memory function—as well as those with anti-inflammatory and anticoagulant properties:

Finally, by preventing blood clots and "thinning" the blood, anticoagulants can help prevent strokes that result in disabling vascular dementia, while improving sluggish circulation in brain areas deprived of the oxygen and glucose they require for daily functioning.

We will now examine several nutritional supplements that play critically important roles in supporting brain health. Uridine boosts brain energy while protecting nerve cells and promoting their regeneration. GPC (glycerophosphocholine) and phosphatidylserine increase acetylcholine synthesis. Vinpocetine is a powerful anti-inflammatory and anticoagulant agent. Ashwagandha prevents the degradation of brain cells and acetylcholine. Blueberries and grape seed extract fight inflammation and toxic beta-amyloid buildup in the brain.

Uridine: Boosting Brain Cell Communication

One of the most promising biological compounds for enhancing healthy brain structure and cognitive function is uridine. Found in living organisms ranging from humans to bacteria, uridine is a nucleoside, or a combination of a sugar (ribose) with uracil. Nucleosides such as uridine are building blocks for RNA, the biochemical cousin of DNA that serves as a template in gene expression. Uridine is so important to brain development that it is included in human infant formulas. Animal experiments have demonstrated that rats incorporate uridine in their brain RNA during learning exercises.10 However, uridine is essential for effective brain function throughout the human life span.11,12

When orally ingested, uridine crosses the blood-brain barrier to reach brain cells. Once this happens, it increases levels of CDP-choline, which is required for the synthesis of phosphatidylcholine and ultimately of the essential neurotransmitter acetylcholine. Evidence suggests that increased brain levels of phosphatidylcholine improve cognitive function.13,14 Growing evidence also indicates that uridine is a major building block for the synthesis of nerve cell membranes, suggesting that it could play a role in managing various neurodegenerative diseases.15

Neuroscientists consider gerbils to be an excellent animal model for studying diseases of the human brain. When gerbils were given a combination of uridine, choline, and the omega-3 fatty acid DHA (docosahexaenoic acid)—all important components of cell membranes—their brain levels of phosphatidylcholine rose an impressive 45%.16 Because Alzheimer's patients demonstrate damaged synapses and depleted levels of uridine, DHA, and choline, this finding is particularly striking. Phosphatidylcholine is crucial for nerve cell growth and repair, and specifically for optimal function of the synapses, the junctions where nerve cells communicate with nerve and other types of cells.17 This supplement combination also increased proteins critical to nerve function by 38-102%, suggesting that it actually increased the number of nerve cell membranes containing synapses.16

Since the brains of Alzheimer's patients contain fewer, smaller synapses, reduced levels of synaptic proteins, and decreased cell membrane components—including choline and DHA—it stands to reason that supplementing with these agents may be useful in treating the disease.16 Scientists are now conducting human clinical trials to assess the effects of this nutrient combination in treating Alzheimer's.

Uridine also enhances the growth of neurites, which are projections from nerve cells that facilitate the cells' connections with other brain cells. Uridine also helps stabilize nerve cell membranes18 and enhances their release of the crucial neuro-transmitter dopamine, boosting the brain's ability to transmit messages.17

Animal experiments suggest that uridine promotes optimal cognitive function even in instances of memory impairment. In rats with hypertension-induced memory loss, supplemental uridine and choline improved their selective attention and spatial learning abilities.19 Similarly, uridine protected against malnutrition-induced impairment of memory and learning by preventing adverse changes in the hippocampus,20 the brain area considered essential for long-term memory and associated with the degenerative changes seen in Alzheimer's disease.

Another animal study suggests that in addition to its effects on brain structure and function, uridine may help promote improved mood. Rats given uridine and omega-3 fatty acids displayed improved performance on a behavioral test demonstrated to predict antidepressant effects in humans. Remarkably, the combined antidepressant effect was similar to that of prescription antidepressant agents.21

Abundant evidence thus suggests that uridine supports healthy nerve cell membranes and neurite outgrowth, as well as the release of brain neurotransmitters. These effects have been linked with improvements in memory, learning ability, and mood, and hold promise in preventing and managing neurodegenerative diseases such as Alzheimer's.

GPC: Stabilizing and Reversing Cognitive Impairment

GPC (glycerophosphocholine), a compound related to phosphatidylcholine, has the remarkable ability to forestall, stabilize, and even partially reverse cognitive impairment in the early stages of senile dementia.6,22 Available in Europe only as the prescription drug Gliatilin®, GPC can be obtained over the counter as a dietary supplement in the US. GPC has been found to be well tolerated, with few side effects.6

Medically, Alzheimer's is usually treated with drugs such as donepezil (Aricept®) and rivastigmine (Exelon®) that block the enzyme acetylcholinesterase from breaking down acetylcholine at the synapse, or connection between two nerves. Known as acetylcholinesterase inhibitors, these medications allow acetylcholine to act at the synapse for longer periods, thereby counteracting the reduced activity in nerve pathways that use acetylcholine.

Unlike drugs that inhibit the breakdown of acetylcholine, GPC actually stimulates the manufacture of new acetylcholine.

Promising animal studies suggest that GPC may help prevent memory loss in humans. Compared to controls, aging rats fed GPC lose fewer nerve connections in the hippocampus, the brain region crucial for memory and learning.23-25 The GPC-fed rats were also protected against a decline in nerve pathways utilizing acetylcholine26 and impairment of higher learning and memory capacities.27

GPC demonstrates its versatility by boosting brain function via several mechanisms. It stimulates release of the neurotransmitter GABA (gamma-aminobutyric acid), making more GABA available to brain cells. Dwindling levels of GABA in the elderly may partly account for early cognitive impairment, contributing to the dementia, mood disorders, and psychoses seen in degenerative brain conditions such as Alzheimer's and Huntington's disease.29

Clinical trials have confirmed the benefits of GPC seen in the laboratory studies. In a multicenter study of patients with probable Alzheimer's disease, GPC improved cognition and was well tolerated.30 In another large, multicenter Italian study of more than 2,000 patients with recent stroke or "mini-stroke" (transient ischemic attack) who received GPC for six months, 71% had normal cognitive function or only mild forgetfulness when the study ended. The authors concluded that the trial confirms GPC's efficacy in supporting the cognitive recovery of patients with acute stroke or mini-stroke.31

In a well-controlled, multicenter study in Mexico, GPC significantly improved cognitive function in 261 patients with mild-to-moderate Alzheimer's disease.32 The patients were randomly assigned to receive either 1200 mg of GPC or placebo daily for six months, and both groups were similarly impaired before entering the study.

On several standardized psychological tests of cognitive function, patients who received GPC scored better than those who received placebo. A measure of cognitive function substantially improved in the GPC group, but worsened in the placebo group. Compared to placebo, the GPC group also fared better in behavioral improvement and standardized physician ratings. The study findings support GPC's efficacy in treating the cognitive symptoms of dementia disorders such as Alzheimer's.32

What makes these results particularly encouraging is that they resemble those obtained through the use of Alzheimer's drugs such as Aricept® and Exelon®. Unlike those drugs, however, GPC is easy to tolerate, with fewer side effects.32

In a review of 13 published clinical trials involving 4,054 patients with age-related memory loss or vascular dementia caused by stroke or mini-stroke (transient ischemic attack), scientists concluded that GPC produced consistent improvements in memory and attention, and significantly improved patients' clinical condition, even when tested in a variety of experimental settings.6

The scientists also noted that GPC effectively relieved the cognitive symptoms of chronic cerebral deterioration. Furthermore, patients using GPC demonstrated clinical results that were equivalent or superior to control groups under active pharmaceutical treatment. The researchers hope to conduct further studies to examine GPC's role in supporting the recovery of patients who have suffered a stroke.

Phosphatidylserine: A Versatile Memory Enhancer

Phosphatidylserine plays an extraordinarily varied role in supporting brain health. It enhances the availability of acetylcholine,33 lowers levels of the stress hormone cortisol, and promotes the release of dopamine, an important neurotransmitter known to improve mood and movement control.

Phosphatidylserine also supports the function of many vital enzymes, acts as an antioxidant to combat free-radical damage, and quells inflammation that can exert deleterious effects in the brain.34 In Europe and Japan, phosphatidylserine is sold as a prescription drug to treat memory and learning dysfunction, but it is available as a nutritional supplement in the United States.

Humans manufacture phosphatidylserine to maintain the structure and function of cell membranes, but its production in the body declines with advancing age. Aged rats with cognitive deficits have demonstrated decreased phosphatidylserine in the hippocampus,35 and subjects with a genetically determined type of cognitive deficit exhibit low phosphatidylserine levels in nerve cell membranes.36

When aged rats were given phosphatidylserine for two months, their performance on an age-related memory impairment test improved significantly, indicating better memory function. Phosphatidylserine supplementation restored the rats' acetylcholine release and energy metabolism in nerve endings to levels typically seen in young rats.37

Further animal studies suggest that phosphatidylserine acts as an antidepressant agent.38 This finding could have far-ranging implications for elderly humans, in whom depression is often confused clinically with cognitive impairment.

By stimulating acetylcholine production,39 phosphatidylserine has proven useful in clinical trials of patients with cognitive impairment.5 These include an open study in patients with age-related cognitive decline,40 well-controlled, randomized trials in patients with senile dementia,41 and a study in Alzheimer's patients who exhibited the stiffness and rigidity associated with Parkinson's disease.42

A review of the available research indicates that while phosphatidylserine may help improve memory in elderly patients,43 its effects may be most pronounced in early cognitive impairment44—an observation that underscores the vital importance of beginning supplementation with brain-nourishing nutrients like phosphatidylserine early in life.

A leading scientist at the Alzheimer's Prevention Foundation has suggested that phosphatidylserine may be a useful component in a lifestyle and nutrition program aimed at preventing Alzheimer's disease.45 He concludes that memory loss is not an inevitable consequence of aging, and that Alzheimer's can be prevented or reversed using an integrated approach that includes phosphatidylserine and other brain-supportive nutrients.

Although phosphatidylserine is generally safe and well tolerated,46,47 it may increase the blood-thinning effect of heparin, and therefore should not be used with medications that thin the blood without consulting a physician.48

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